Pain, either acute or chronic, is a source of everyday agony for millions of patients. Understanding the components of nociception--the detection of harmful stimuli by sensory neurons-would greatly facilitate development of treatments for pain. In this proposal, I will investigate the development of the trigeminal sensory ganglia, the major organ for sensing potentially harmful (noxious) stimuli to the head. During development, a trigeminal sensory neuron (TGN) extends two types of projections: a peripheral axon and a central axon. The peripheral axon innervates the skin of the head and receives sensory stimuli;the central axon, in contrast, projects to deep brain regions and synapses on to neurons. The correct pattern of axonal arborization is crucial forTGN's function, but the mechanism by which this is achieved is unclear. To address these questions, I adopted the zebrafish TGN as a model system because it allows direct visualization and manipulation of growing axonal arbors in live, behaving animals at the single cell level. Specific Aim 1: The roles of neural activity in peripheral axonal arborization. To investigate the roles of neural activity in peripheral axon arborization, I will inactivate individual TGNs and determine their arborization pattern with respect to their neighbors. Specific Aim 2: The role of neurotrophins in peripheral axonal arborization. To investigate the role of neurotrophin signaling on the size and density of the peripheral axonal arbors, I will block or activate Trk receptors and determine the arborization pattern of TGNs. Specific Aim 3: Central axon projection of TGN neurons. To determine the central projection pattern of TGNs, I will use photoconvertible and photoactivatable fluorescent proteins to label central axons of individual neurons and determine whether there is topographic projection that corresponds to the receptive area in the head. Relevance: Understanding the components of nociception would greatly facilitate development of treatments for pain. I propose to investigate the development of the trigeminal sensory ganglia, the major organ for sensing noxious stimuli to the head.